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HF Risk Assessment Using Biomarkers in Patients With AF
Quick Takes
- In patients with AF, elevated NT-proBNP, hs-cTnT, and GDF-15 levels are independently associated with a composite of hospitalizations for HF and CV death.
- The biomarkers improve risk prediction when added to clinical models.
- The value of biomarker use was seen across HF history, AF type, and LVEF subgroups.
Study Questions:
What is the value of specific biomarkers for heart failure (HF) risk stratification in patients with atrial fibrillation (AF)?
Methods:
For this study, individual patient-level data were used from the COMBINE-AF study (pooled data from four randomized trials comparing direct oral anticoagulants to warfarin; baseline biomarker data were available for three of these trials [ARISTOTLE, ENGAGE AF-TIMI 48, RE-LY] and used in this analysis). Biomarkers of interest were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth-differentiation factor (GDF)-15. The primary endpoint examined was a composite of hospitalization for HF (HHF) or cardiovascular (CV) death. Secondary endpoints were HHF and HF-related death.
Results:
A total of 32,041 patients from the three randomized trials had complete biomarker data available. This cohort had a median age of 71 years (interquartile range [IQR], 64-77) and were 63.3% male. Persistent/permanent AF was present in 77.0% of patients and a history of HF in 41.6% of patients. Median level of NT-proBNP was 760 pg/mL (IQR, 376-1351), hs-cTnT was 12 ng/L (IQR, 8.1-18.5), and GDF-15 was 1495 pg/mL (IQR, 1060-2201). Over 32 months of follow-up, the annualized rates of HHF or CV death, HHF, and HF-related death for the overall cohort were 4.04%, 2.13%, and 0.42% patients/year, respectively.
For the primary and secondary outcomes, higher levels of the three biomarkers were associated with graded increases in risk for HHF or CV death, HHF, and HF-related death. After multivariable adjustment, the three biomarkers were each independently associated with HHF or CV death (NT-proBNP: hazard ratio [HR] per 1-standard deviation [SD] of 1.68, 95% confidence interval [CI] 1.59-1.77; hs-cTnT: HR per 1-SD of 1.39, 95% CI 1.33-1.44; GDF-15: HR per 1-SD of 1.20, 95% CI 1.15-1.25). While all three biomarkers contributed to risk assessment, NT-proBNP and hs-cTnT provided a greater contribution than GDF-15. Results were similar for the secondary outcomes of HHF and HF-related death. Results were also similar across the HF history, AF type, and left ventricular ejection fraction (LVEF) subgroups.
Conclusions:
In patients with AF, elevations in the biomarkers NT-proBNP, hs-cTnT, and GDF-15 are independently associated with a composite of HHF and CV death. The biomarkers incrementally add to the risk assessment for HF events beyond clinical models.
Perspective:
In patients with risk factors for HF, including a history of AF, use of established biomarkers like NT-proBNP are guideline recommended for HF risk prediction. The results of this study suggest that in a select AF population, use of hs-cTnT may provide independent and equally as important prognostic information. GDF-15 was also assessed and added to risk assessment, but to a lesser degree than NT-proBNP and hs-cTnT. These biomarkers used together may help provide a more complete picture of risk and pathophysiology as they provide different information on cardiac myocyte stretch, injury, and inflammation. Future work will need to focus on how these biomarkers apply to a generalized at-risk for HF population, best ways to incorporate biomarkers into current HF risk prediction models, and what impact this information has on ability to modify future risk with current and future interventions.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Atrial Fibrillation, Biomarkers, Heart Failure
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